Platelets and fibrinogen play integral roles in the formation of blood clots (thrombi). Platelets first adhere to macromolecules in the subendothelial regions of an injured blood vessel; they then aggregate to form the nidus of a thrombus. Platelet aggregation is mediated by fibrinogen binding to the activated platelet membrane glycoprotein IIb/IIIa (GP IIb/IIIa) receptor. The platelets stimulate local activation of plasma coagulation factors, which leads to the conversion of fibrinogen bound to GP IIa/IIIb receptor to fibrin monomers which polymerize to form the matrix (fibrin clot) of a thrombus.
Epidemiological studies have shown that elevated levels of plasma fibrinogen are associated with acute myocardial infarction, ischemic heart disease, coronary mortality, stroke in men, deep vein thrombosis and throbophlebitis (Meade et al., Eur. Heart J. 16 Suppl A:31-35 (1995); Meade et al., Br. Med. Bull. 33:283-288 (1977); Meade et al., Lancet ii:533-537 (1986); Wilhelmsen et al., N. Engl. J. Med. 311:501-505 (1984); Kannel et al., JAMA 258:1183-1186 (1987); Stone and Thorp, J. R. Coll. Gen. Pract. 35:565-569 (1985); Balleisen et al., Lancet ii:461 (1987); Lee et al., J. Clin. Epidemiol. 43:913-919 (1990); Moller and Kristensen, Arterioscler. Thromb. 11:344-350 (1991); Broadhurst et al., Atherosclerosis 85:169-173 (1990); Handa et al., Atherosclerosis 77:209-213 (1989)).
Increased levels of platelet GP IIa/IIIb receptors are also associated with acute myocardial infarction (Brown et al., Eur. J. Clin. Invest. 24 Suppl. 1:9-15 (1994); Giles et al., Eur. J. Clin. Invest. 24:69-72 (1994)).
Platelets play an important role in the development of the atherosclerotic lesions that typically underlie coronary artery disease, aortic aneurysm, arterial disease of the lower extremities and cerebrovascular disease.
Thus, elevated circulating fibrinogen and/or platelet levels are independent risk factors that are at least as significant as cholesterol or hypertension for vascular diseases, such as coronary heart disease and cerebrovascular disease.